Patrick Daly

DocwireNews

Bruton&rsquo;s tyrosine kinase (BTK) inhibitors and mouse double minute 2 (MDM2) inhibitors are both targeted therapies used to treat patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). BTK inhibitors disrupt proliferation and release malignant B cells into circulating peripheral blood, while MDM2 inhibitors improve apoptosis of TP53 wild-type B cells.Researchers of a phase 1b/2 study explored whether combining navtemadlin, an MDM2 inhibitor, with acalabrutinib, a BTK inhibitor, could improve treatment response in BTK inhibitor-na&iuml;ve patients with relapsed or refractory (R/R) CLL or SLL. Results from the phase 1b portion of the study were presented at the <a href="https://ehaweb.org/congress/eha2023-hybrid-congress/eha2023/" target="_blank" rel="noopener">European Hematology Association 2023 Hybrid Congress</a>.Lead author Dr. John Byrd reported navtemadlin plus acalabrutinib had acceptable safety and showed no dose-limiting toxicities during 3+3 dose escalation. The team also identified a recommended phase 2 dose of 240 mg and reported &ldquo;encouraging preliminary activity&rdquo; in the study&rsquo;s cohort.<h2>Combining Targeted Therapies in CLL, SLL</h2>The primary end points of the phase 1b portion were recommended dose for phase 2 and the rates of complete remission (CR) and CR with incomplete count recovery (CRi). Secondary end points included overall response rate (ORR), duration of response, safety, and tolerability.The study tested 3 doses of once-daily navtemadlin administered on days 1 to 7 of 28-day cycles in combination with continuous twice-daily acalabrutinib 100 mg. A 28-day lead-in of acalabrutinib monotherapy was tested but closed after the first 6 participants. As of February 2023, the phase 1b portion had enrolled 15 participants at 10 centers in 6 countries.The cohort had a median age of 64 years, Eastern Cooperative Oncology Group scores of 0 or 1, a median of 1 prior line of therapy, and nearly half had unmutated immunoglobulin heavy chain disease. Additionally, 73% of the patients had Binet stage B/C disease, 27% had del11q, and none had del17p.Among the 7 patients treated with the recommended phase 2 dose of 240 mg for 6 or more months, the ORR for partial response or better was 86%, and 2 patients achieved CR or CRi by week 32. Researchers added that all 6 patients who had initiated navtemadlin and acalabrutinib concurrently demonstrated minimal lymphocytosis and rapid reductions in absolute lymphocyte counts.All participants reported treatment-emergent adverse events (TEAEs). The most common TEAEs of any grade and any cause were nausea (80%), diarrhea (60%), constipation (47%), fatigue (40%), vomiting (40%), headache (40%), thrombocytopenia (33%), cough (27%), and dizziness (27%). Grade 3 or 4 TEAEs occurred in 73% of participants, with the most common being diarrhea, thrombocytopenia, neutropenia (all 13%). No grade 5 events occurred.Ultimately, the study&rsquo;s authors concluded that navtemadlin plus acalabrutinib had an acceptable safety profile with promising preliminary activity in BTK inhibitor-na&iuml;ve patients with relapsed or refractory CLL or SLL.View More <a href="https://docwirenews.com/category/eha-2023">Highlights from the EHA 2023 Hybrid Congress</a>

Sara Nunnery, MD, MSCI

Reclassifying HER2: What Oncologists Need to Know About HER2-Low and -Ultralow Breast Cancer

HER2 Breast Cancer

Jeffrey Perl, MD

Joel M. Topf, MD, FACP

Thoughts From the 2025 Lazarus Award Winner

NKF Spring Clinical Meetings 2025

Brandon Twyford

DESTINY-Breast09 Demonstrates First-Line Superiority of Enhertu Plus Pertuzumab in HER2-Positive Metastatic Breast Cancer

Latest News

Navtemadlin Plus Acalabrutinib in R/R CLL, SLL

EHA 2023

Preliminary data from the EHA2023 Hybrid Congress suggested navtemadlin plus acalabrutinib had acceptable safety and promising activity in a phase1b cohort of patients with CLL.

About Us

Editorial Policy

Advertising

Contact Us

eNewsletters

Contribute

Career Center

MashupMD

Blood Cancers Today

Cancer Nursing Today

GU Oncology Now

Urban Health Today

Bile Duct Cancer

Colorectal Cancer

Gastroesophageal Cancer

Gastric Cancer

GEP-NETs

GIST

Liver Cancer

Pancreatic Cancer

GI Oncology Now

Anemia

Deep Vein Thrombosis

Essential Thrombocythemia

Hemophilia

Immune Thrombocytopenic Purpura

Myelodysplastic Syndromes

Myelofibrosis

Myeloproliferative Neoplasms

Polycythemia Vera

Pulmonary Embolism

Sickle Cell Disease

Thrombocytopenia

Thrombophilia

Thrombosis

Thrombotic Thrombocytopenic Purpura

Venous Thromboembolism

von Willebrand Disease

Heme Today

Acute Kidney Injury

ADPKD

Anemia and Kidney Disease

Chronic Kidney Disease

COVID-19 and Kidney Disease

Diabetes and Hypertension

End-Stage Renal Disease

Gout

Hyperkalemia

IgAN

Kidney Transplantation

Metabolic Acidosis

Nephrology Times

HR Breast Cancer

Triple-Negative Breast Cancer

Genetics & Breast Cancer

Breast Cancers Today

Atherosclerotic Disease

Atrial Fibrillation

Heart Failure

Hypertension

Interventional Cardiology

Lipid Management

Practice Tips With Dr. Lichaa

Preventive Cardiology

Stroke

Cardiology

Breast Cancer

Gynecologic Cancer

Head and Neck Cancer

Skin Cancer

Oncology

Sleep

Urology

Diabetes

Ophthalmology

— Demodex Blepharitis

Neurology

Rheumatology

Gastroenterology

Pulmonology

Infectious Diseases

— HIV

Health and Wellness

Lupus

Future of Medicine

Orthopedics

Pharmacology

Career News

More

Conferences

CardioNerds

The Sleep Source With Dr. Morse

Rheumatology Rounds With Dr. Maheswaranathan

Partners

Expert Interviews

Subscribe